Counteraction between Astrin-PP1 and Cyclin-B-CDK1 pathways protects chromosome-microtubule attachments independent of biorientation.
Springer Science and Business Media LLC
MetadataShow full item record
Song, X., Conti, D., Shrestha, R. L., Braun, D., & Draviam, V. M. (2021). Counteraction between Astrin-PP1 and Cyclin-B-CDK1 pathways protects chromosome-microtubule attachments independent of biorientation.. Nat Commun, 12 (1) https://doi.org/10.1038/s41467-021-27131-9
Defects in chromosome-microtubule attachment can cause chromosomal instability (CIN), frequently associated with infertility and aggressive cancers. Chromosome-microtubule attachment is mediated by a large macromolecular structure, the kinetochore. Sister kinetochores of each chromosome are pulled by microtubules from opposing spindle-poles, a state called biorientation which prevents chromosome missegregation. Kinetochore-microtubule attachments that lack the opposing-pull are detached by Aurora-B/Ipl1. It is unclear how mono-oriented attachments that precede biorientation are spared despite the lack of opposing-pull. Using an RNAi-screen, we uncover a unique role for the Astrin-SKAP complex in protecting mono-oriented attachments. We provide evidence of domains in the microtubule-end associated protein that sense changes specific to end-on kinetochore-microtubule attachments and assemble an outer-kinetochore crescent to stabilise attachments. We find that Astrin-PP1 and Cyclin-B-CDK1 pathways counteract each other to preserve mono-oriented attachments. Thus, CIN prevention pathways are not only surveying attachment defects but also actively recognising and stabilising mature attachments independent of biorientation.
Chromosomes, Kinetochores, Microtubules, Genomic Instability, Resorcinols, Alcian Blue, Phenazines, Phenothiazines, CDC2 Protein Kinase, Receptors, Neuropeptide Y, Chromosome Segregation, Cyclin B1, Spindle Apparatus, Aurora Kinase B, Spindle Poles
RCUK | Biotechnology and Biological Sciences Research Council (BB/T017716/1, BB/W002698/1, R01003X/1)
Queen Mary University of London (SBC9DRA2)
Cancer Research UK (C28598/A9787)
Medical Research Council (MR/K50127X/1)
Biotechnology and Biological Sciences Research Council (BB/T017716/1, R01003X/1, BB/W002698/1)
External DOI: https://doi.org/10.1038/s41467-021-27131-9
This record's URL: https://www.repository.cam.ac.uk/handle/1810/333073
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/